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MCL-1Matrix maintains neuronal survival by enhancing mitochondrial integrity and bioenergetic capacity under stress conditions.
Anilkumar, Ujval; Khacho, Mireille; Cuillerier, Alexanne; Harris, Richard; Patten, David A; Bilen, Maria; Iqbal, Mohamed Ariff; Guo, Ding Yuan; Trudeau, Louis-Eric; Park, David S; Harper, Mary-Ellen; Burelle, Yan; Slack, Ruth S.
Afiliación
  • Anilkumar U; University of Ottawa Brain and Mind Research Institute, Department of Cellular and Molecular medicine, University of Ottawa, Ottawa, ON, Canada.
  • Khacho M; Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON, Canada.
  • Cuillerier A; Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada.
  • Harris R; University of Ottawa Brain and Mind Research Institute, Department of Cellular and Molecular medicine, University of Ottawa, Ottawa, ON, Canada.
  • Patten DA; Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON, Canada.
  • Bilen M; University of Ottawa Brain and Mind Research Institute, Department of Cellular and Molecular medicine, University of Ottawa, Ottawa, ON, Canada.
  • Iqbal MA; University of Ottawa Brain and Mind Research Institute, Department of Cellular and Molecular medicine, University of Ottawa, Ottawa, ON, Canada.
  • Guo DY; Department of Pharmacology & Physiology and Neurosciences, Université de Montréal, Montréal, QC, Canada.
  • Trudeau LE; Department of Pharmacology & Physiology and Neurosciences, Université de Montréal, Montréal, QC, Canada.
  • Park DS; Department of Clinical Neurosciences, and Cell Biology and Anatomy, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
  • Harper ME; Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON, Canada.
  • Burelle Y; Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada. yburell2@uottawa.ca.
  • Slack RS; University of Ottawa Brain and Mind Research Institute, Department of Cellular and Molecular medicine, University of Ottawa, Ottawa, ON, Canada. rslack@uottawa.ca.
Cell Death Dis ; 11(5): 321, 2020 05 05.
Article en En | MEDLINE | ID: mdl-32371858
Mitochondria play a crucial role in neuronal survival through efficient energy metabolism. In pathological conditions, mitochondrial stress leads to neuronal death, which is regulated by the anti-apoptotic BCL-2 family of proteins. MCL-1 is an anti-apoptotic BCL-2 protein localized to mitochondria either in the outer membrane (OM) or inner membrane (Matrix), which have distinct roles in inhibiting apoptosis and promoting bioenergetics, respectively. While the anti-apoptotic role for Mcl1 is well characterized, the protective function of MCL-1 Matrix remains poorly understood. Here, we show MCL-1OM and MCL-1Matrix prevent neuronal death through distinct mechanisms. We report that MCL-1Matrix functions to preserve mitochondrial energy transduction and improves respiratory chain capacity by modulating mitochondrial oxygen consumption in response to mitochondrial stress. We show that MCL-1Matrix protects neurons from stress by enhancing respiratory function, and by inhibiting mitochondrial permeability transition pore opening. Taken together, our results provide novel insight into how MCL-1Matrix may confer neuroprotection under stress conditions involving loss of mitochondrial function.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Supervivencia Celular / Proteína 1 de la Secuencia de Leucemia de Células Mieloides / Mitocondrias / Neuronas Límite: Animals / Humans Idioma: En Revista: Cell Death Dis Año: 2020 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Supervivencia Celular / Proteína 1 de la Secuencia de Leucemia de Células Mieloides / Mitocondrias / Neuronas Límite: Animals / Humans Idioma: En Revista: Cell Death Dis Año: 2020 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido